Fiber-optic probes make it possible to collect optical information such as Raman spectra without having to place the material being characterized inside a spectrometer housing. Such probes therefore simplify the interfacing of spectroscopic systems to samples under investigation, and allow analytical instruments to be located remotely from environments in need of spectroscopic monitoring.
The first remote fiber optic probes for Raman spectroscopy were reported by the McCreery group in the early 1980's. Their design used a single optical fiber to deliver laser light to the sample and a single optical fiber to collect light scattered by the sample. More specifically, divergent laser light from the laser delivery fiber was used to illuminate the sample, and light scattered from the sample within the acceptance cone of the collection fiber was transmitted back to the spectrograph. The efficiency of exciting and collecting Raman photons from any individual point in the sample was poor, but the integrated Raman intensity over the unusually large analysis volume compared favorably with the more traditional imaged illumination and collection configurations.
Several improvements to the McCreery Raman probe have more recently been reported. Instead of using just one collection fiber, multiple fibers have been used to increase the collection efficiency. For example, 6 fibers, each having the same diameter as the excitation fiber, may be grouped around the excitation fiber to form a single circular layer, as shown in U.S. Pat. No. 4,573,761. The performance of the McCreery type probe can also be modified for improved collection efficiency and/or working distance by changing the overlap between the emission cone of the excitation fiber and the collection cones of the collection fibers. An early realization of this idea, as disclosed in U.S. Pat. No. 4,573,761, angled the collection fibers such that their optic axes intersected the optic axis of the illumination fiber. This increased the overlap of the excitation and collection cones close to the tip of the fiber probe, where the excitation and collection of Raman photons was most efficient.
One further variation of the McCreery probe design is to use collection fibers having a different diameter than the excitation fiber. This additional variable is useful for changing the working distance of the probe and the fiber coupling to the spectrograph. However, one disadvantage of existing probes in their relatively small spot size. The large intensity of the small spot limits applications, often requiring scanning to cover a larger sample area. The high intensity of the small spot also precludes certain temperature-sensitive applications, including direct human contact. One of the most significant limitations of existing bundle probe designs is that they are not confocal, there is not complete overlap of the excitation light with the collection aperture.
Commonly assigned U.S. Pat. No. 7,148,963 describes a compact Raman/fluorescence confocal probe which is capable of collecting spectra from an area of 1 mm or greater, preferably 3-12 mm or more, as compared to current instruments which utilize spot sizes on the order of 2-60 microns. The fact that the large data collection area is confocal with the excitation light vastly improves the signal efficiency of the overall probe.
The larger spot size facilitates the collection of statistically useful data from inhomogeneous and laser-sensitive samples, among other applications. Potential pharmaceutical tablet applications include dosage level measurements, confirmation of desired polymorphic form, identification of unwanted polymorphic and amorphous forms of the active ingredient, as well as online and at-line quality-control (QC) monitoring opportunities. Other applications include tablet identification as a forensic tool to identify counterfeit pharmaceutical products; granulation and blend uniformity, tablet coating uniformity and active content within the coating for improved formulation via better process understanding
Another area of interest is using the lower laser energy density provided by expanding the laser to up to 10 mm or more to analyze skin and the effects of cosmetics on skin without causing damage to the skin. The probe conforms to the ANSI standards and is therefore skin safe.
Previously implemented systems developed and demonstrated by Kaiser Optical Systems, Inc. use diode lasers (i.e., 785 nm, 830 nm) and large array CCD detectors (i.e., 1024 pixels by 256 pixels) allowing Raman spectra (Stokes shifted) to be collected in both reflectance and transmission of sufficient volume of sample to be representative of the whole sample. While the use of a large-area CCD provides distinct advantages, in some applications the excitation wavelengths generate sufficient fluorescence to limit the detection of low concentrations of critical components.
To reduce fluorescence from certain natural solid components (i.e., micro crystalline silica in pharmaceutical tablets) a near-infrared laser may be used in conjunction with an InGaAs detector combination to eliminate or reduce significantly fluorescence from natural materials such as Micro Crystalline Silica. The problem with such a configuration is that affordable InGaAs detectors are configured as a linear array, making them acceptable for moving liquid samples but not applicable to large area solid samples.
An outstanding need remains, therefore, for a Raman probe that collects spectra over a wide spot area while significantly reducing if not eliminating fluorescence from certain solid components.